A	B	C	D	E	F	G	H	I	J	K	L
1	Main
2		Brand Name	Eylea
3		Generic Name	aflibercept
4		Mechanism	VEGF A/B trap. Intraocular half life estimated to be 65% longer than Lucentis, but on par with Avastin.
5		Indication	AMD
6		Competition	Lucentis, Avastin, Macugen.
7		Economics	Bayer 50/50 outside US, all Regeneron in the US.
8		Administration	Uses a direct formulation specifically designed for direct injection into a patients eye
9		Clinical Trials	Phase III head-to-head vs Lucentis in 1H07?
10
11			Phase 3 - VIEW-1
12			n = 1217, double blinded, radomized, Lucentis control
13			4 groups. Eylea 2 mg/q4 weeks, 0.5 mg/q4 weeks, 2 mg/8 weeks, Lucentis 0.5 mg/q4 weeks.
14			Primary endpoint was vision maintenance at 1 year, measured by letters readable.
15			Secondary endpoint was mean change in BCVA.
16			% completing 52 weeks					Luc	2mg/q4wk Eyl	0.5mg/q4wk Eyl	2mg/q8wk Eyl
17			Luc:		0.93		n	304	304	301	301
18			2mg/q4wk Eyl		0.96		Age	78	78	78	78
19			0.5mg/q4wk Eyl		0.91		Female %	57	64	56	59
20			2mg/q8wk Eyl		0.91		ETDRS BCVA	54	55	56	56
21							Vision maint at 1 yr	0.94	0.95	0.96	0.96
22							Change vis acquity 1 yr	8.1	10.9	6.9*	7.9*	* p = NS vs luc
23							% gaining >15 letters	31	38	25	31
24
25			Phase 3 - VIEW-2
26			n = 1240, double blinded, radomized, Lucentis control
27			4 groups. Eylea 2 mg/q4 weeks, 0.5 mg/q4 weeks, 2 mg/8 weeks, Lucentis 0.5 mg/q4 weeks.
28			Primary endpoint was vision maintenance at 1 year, measured by letters readable.
29			Secondary endpoint was mean change in BCVA.
30			% completing 52 weeks
31			Luc:		0.91			Luc	2mg/q4wk Eyl	0.5mg/q4wk Eyl	2mg/q8wk Eyl
32			2mg/q4wk Eyl		0.9		n	291	309	296	306
33			0.5mg/q4wk Eyl		0.88		Age	73	74	75	74
34			2mg/q8wk Eyl		0.91		Female	58	57	50	57
35							ETDRS BCVA	54	53	52	52
36							Vision maint at 1 yr	0.94	0.95	0.96	0.96
37							Change vis acquity 1 yr	9.4	7.6*	9.7*	8.9*	* p = NS vs luc
38							% gaining >15 letters	34	29	35	31
39
40			FDA action
41			Filed BLA Feb 2011, and receive priority review. PDUFA date of Aug. 28, 2011.
42			June 2011, Ad Panel voted unanimously (10 to 0) to approve Eylea for wet AMD at the 2 mg/q8 week dose, following 3 initial doses given q4 weeks.
43			Aug 2011, PDUFA date extended to Nov. 18, 2011, based on responses to questions on CMC section tha FDA considered major amendements.
44
45			CATT study, Lucentis comparison with Avastin
46			Martin et al., NEJM, 2011, 364, 1897.
47			n = 1208, single blind, non-inferiority study
48			Dosing was monthly or as needed, primary endpoint was change in visual acquity at 1 year.
49			Monthly, 2 were equivalent in visual acquity.
50			No stat sig differecnes in AEs
51			Dosing as needed was equivalent to monthly dosing for both.
52			Given as needed, Lucentis afforded improvement of 6.8 letters, compared to 5.9 for Avastin (p = 0.45).
53			Average # of injections/ year is <7.
54			An editorial by Rosenfeld in NEJM (2011, 364, 1966) suggested that even in the absence of long term safety data there is no reason not to use Avastin, and challenges that healthcare rpvodiers will need to justify uise of the more expensive Lucentis.
55
56			Phase II in AMD - monthly dosing for 12 weeks - ARVO 2008 32-week update
57			97% did not require additional dose at week 16.
58
59			Phase II in AMD - March 2007
60			5.9 letter improvement.
61			5.4 letter improvement and 9.0 letter improvement at 52 weeks at 0.5mg and 2.0mg.
62			This compares favorably with 0.5 letter and 2.0 letter improvement at 52 weeks for 0.3mg and 0.5mg of Lucentis in SAILOR.
63
64			18 patients with the neovascular form of wet amd
65			patients demonstrated rapid, substantial and prolonged (up to 6 week) reductions in retinal thickness as measured by optical coherene topography. Lucentis only stabilizes retinal lesions.
66			patients received a single dose of VEGF trap at levels up to 2mg intravitreally
67			maximum tolerated dose has not yet been reached, and no evidence of ocular inflamation
68			additional patients are now being tested at the 4mg level